A Phase 1/2, Observer-blind, Randomized, Placebo-controlled Multi-country Study to Assess Safety and Efficacy of GSK Neisseria Gonorrhoeae GMMA (NgG) Investigational Vaccine When Administered to Healthy Adults 18 to 50 Years of Age
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 1,009
- 试验地点
- 24
- 主要终点
- Phase 1: Number of Participants Reporting Any Solicited Administration Site Events
研究概览
简要总结
The aim of this first time in human proof of concept (FTiH-PoC) study was to evaluate safety and reactogenicity, to demonstrate efficacy and to explore immunogenicity of GlaxoSmithKline's (GSK) Neisseria gonorrhoeae generalized modules for membrane antigens (GMMA) (NgG) investigational vaccine compared to placebo (saline).
详细描述
The study included the following parts:
- Phase 1 - Dose-escalation safety lead-in in healthy participants.
- Phase 2 - Efficacy PoC in healthy participants considered at risk for gonorrhea.
The doses to be tested for efficacy would be selected based on the safety evaluation performed during the dose-escalation safety lead-in: in case more than one dose would show tolerability, the highest tolerated dose (HTD) and the dose below the highest tolerated (i.e., 2 doses) would be advanced in the efficacy PoC part of the study and compared versus placebo. In case only the lowest dose shows adequate tolerability, this would be the only dose tested in the PoC versus placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Data was collected in an observer-blind manner.
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria for the dose-escalation safety lead-in part
- •Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
- •Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study-specific procedure.
- •Healthy participants as established by medical history, clinical examination, and laboratory assessment.
- •A participant between and including 18 and 50 years of age at the time of informed consent.
- •Female participants of non-childbearing potential may be enrolled in the study.
- •Female participants of childbearing potential may be enrolled in the study if the participant:
- •has practiced adequate contraception for 1 month prior to study intervention administration, and
- •has a negative pregnancy test on the day of study intervention administration, and
- •has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration series.
- •Inclusion criteria for the efficacy PoC part
- •Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
- •Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study-specific procedure.
- •Healthy participants as established by:
- •For the 2 intensive safety monitoring subsets (i.e., first 30 HIV negative subjects per group followed by first 8 HIV positive subjects per group): medical history, clinical examination, and laboratory assessment.
- •For all the remaining participants: medical history, clinical examination.
- •At risk for gonococcus infections based on sexual behavioral characteristics: this may include men having sex with men, pre-exposure prophylaxis for HIV users, individuals who engage in transactional sex participants with current or past STI diagnosis, participants at time of STI screening or seeking other STI services.
- •A participant between and including 18 and 50 years of age at the time of informed consent. Transgender men and women, and other gender non-conforming people who identify themselves as neither men nor women may be enrolled into the study, based on their risk factors. For the purpose of this study, they will be followed up according to their biological sex (sex at birth), sexual orientation, and genital/sexual anatomy
- •Participants of non-childbearing potential may be enrolled in the study. This includes transmen that have not undergone gender affirming surgery of their genitals.
- •Participants of childbearing potential may be enrolled in the study if the participant:
- •has practiced adequate contraception for 1 month prior to study intervention administration, and
- •has a negative pregnancy test on the day of study intervention administration, and
- •has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration series.
排除标准
- •Medical conditions Dose-escalation safety lead-in part
- •Any clinically significant biochemical laboratory abnormality.
- •Any other clinical condition as determined by the investigator, that may increase participant's risk due to study participation.
- •History of any reaction/hypersensitivity likely to be exacerbated by any component of the study intervention.
- •Confirmed or suspected immunosuppressive/immunodeficient condition, based on medical history and physical examination.
- •Hypersensitivity to latex.
- •Acute/chronic clinically significant pulmonary, cardiovascular, hepatic/renal functional abnormality, as determined by physical examination/laboratory tests.
- •Uncontrolled neurological disorders or seizures.
- •History of invasive meningococcal disease. Efficacy PoC part: HIV negative intensive safety monitoring, HIV negative full enrollment and for all remaining participants
- •Persons under guardianship or trusteeship.
- •Persons deprived of liberty.
- •Gonococcal infection identified within 14 days prior to randomization.
- •Any other clinical condition as determined by the investigator, that may increase participant's risk due to study participation.
- •History of severe allergic reactions and/anaphylaxis, or any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s).
- •Bleeding diathesis / any other condition that would contraindicate intramuscular administration.
- •Confirmed or suspected immunosuppressive/immunodeficient condition, based on medical history and physical examination.
- •Known seropositivity for HIV infection, regardless of viremia and CD4 cell count
- •Hypersensitivity to latex.
- •Acute/chronic clinically significant pulmonary, cardiovascular, hepatic/renal functional abnormality, as determined by physical examination/laboratory tests.
- •Recurrent history/uncontrolled neurological disorders or seizures.
- •History of invasive meningococcal disease.
- •The exclusion criteria depicted above, and the following exclusions criterion applies only for the HIV positive participants (intensive safety monitoring subset and full enrollment of HIV positive participants):
- •Seropositivity for HIV infection if:
- •CD4 cell count < 350 cells/mm3 in the last 6 months
- •viral load > 50cp/ml in the last 6 months
- •participant is not on antiretroviral therapy (ART) for > 3 months or has switched from a different ART in the last 3 months.
- •For both Intensive safety monitoring subset (first 30 HIV negative subjects per group and first 8 HIV positive subjects per group) these criteria apply:
- •Any clinically significant hematological/biochemical laboratory abnormality.
- •Prior/Concomitant therapy Applicable for both the dose-escalation safety lead-in part and the PoC part
- •Use of any investigational/non-registered product other than the study intervention(s) within 30 days before the first dose/planned use during the study period.
- •Previous and planned vaccination with an OMV based Neisseria meningitidis group B vaccine (e.g., Bexsero, MeNZB vaccine or MenBvac at any time prior to first dose and during the entire study period.
- •Planned administration/administration of a vaccine not specified in study protocol within 15 days before the first dose and ending 15 days after the last dose of vaccine administration.
- •Administration of long-acting immune-modifying drugs during the period starting 6 months prior to the first dose of study intervention/planned administration at any time during the study period.
- •Administration of immunoglobulins /any blood products/plasma derivatives during the period starting 3 months before the administration of the first dose of study intervention/planned administration during the study period.
- •Chronic administration (more than 14 days in total) of immunosuppressants/other immune-modifying drugs during the period starting 3 months prior to the first study intervention dose(s). For corticosteroids, this will mean prednisone equivalent ≥20 mg/day for adult participants/ ≥0.5 mg/kg/day. Inhaled and topical steroids are allowed.
- •The following criterion applies only for the PoC part:
- •Chronic/long-term use of systemic antibiotics with an activity against Neisseria gonorrhoeae.
- •Prior/Concurrent clinical study experience applicable for both dose-escalation safety lead-in part and the PoC part Concurrently participating in another clinical study, at any time during the study period, in which the participant has been/will be exposed to an investigational/a non-investigational intervention.
- •Other exclusions applicable for both dose-escalation safety leading part and the PoC part
- •Pregnant/lactating female.
- •Female planning to become pregnant/to discontinue contraceptive precautions before 1 month after completion of the study intervention administration series.
- •Any study personnel/their immediate dependents, family/household members.
- •Lifestyle consideration that may interfere with the conduct of the study/pose additional risks to the rights and wellbeing of participants.
研究组 & 干预措施
Phase 1: Neisseria gonorrhoeae GMMA (NgG) 12.5 micrograms (µg) Group
Participants received 2 doses of NgG 12.5 µg investigational vaccine on Day 1 and Day 61.
干预措施: NgG 12.5 µg investigational vaccine (Biological)
Phase 2: NgG dose below HTD (bHTD; 25 µg) Group
Participants received 2 doses of NgG bHTD (25 µg) investigational vaccine on Day 1 and Day 61. The bHTD is selected based on the safety evaluation performed in Phase 1.
干预措施: NgG 25 µg investigational vaccine (Biological)
Phase 2: Placebo Group
Participants received 2 doses of placebo on Day 1 and Day 61.
干预措施: Placebo (Combination Product)
Phase 1: NgG 25 µg Group
Participants received 2 doses of NgG 25 µg investigational vaccine on Day 1 and Day 61.
干预措施: NgG 25 µg investigational vaccine (Biological)
Phase 1: NgG 50 µg Group
Participants received 2 doses of NgG 50 µg investigational vaccine on Day 1 and Day 61.
干预措施: NgG 50 µg investigational vaccine (Biological)
Phase 1: Placebo Group
Participants received 2 doses of placebo on Day 1 and Day 61.
干预措施: Placebo (Combination Product)
Phase 2: NgG Highest tolerated dose (HTD; 50 µg) Group
Participants received 2 doses of NgG HTD (50 µg) investigational vaccine on Day 1 and Day 61. The HTD was selected based on the safety evaluation performed in Phase 1.
干预措施: NgG 50 µg investigational vaccine (Biological)
结局指标
主要结局
Phase 1: Number of Participants Reporting Any Solicited Administration Site Events
时间窗: From Day 1 to Day 7
Assessed solicited administration site events included injection site pain, erythema (redness), and swelling. Any = occurrence of the event regardless of intensity grade.
Phase 1: Number of Participants Reporting Any Solicited Administration Site Events
时间窗: From Day 61 to Day 67
Assessed solicited administration site events included injection site pain, erythema (redness), and swelling. Any = occurrence of the event regardless of intensity grade.
Phase 1: Number of Participants Reporting Any Solicited Systemic Events
时间窗: From Day 1 to Day 7
Assessed solicited systemic events included headache, fatigue (tiredness), myalgia (muscle pain), arthralgia (joint pain), and fever (pyrexia). Fever is defined as body temperature \>=38ºC; preferred location for measuring the temperature is oral cavity. Any = occurrence of the event regardless of intensity grade.
Phase 1: Number of Participants Reporting Any Solicited Systemic Events
时间窗: From Day 61 to Day 67
Assessed solicited systemic events included headache, fatigue (tiredness), myalgia (muscle pain), arthralgia (joint pain), and fever (pyrexia). Fever is defined as body temperature \>=38ºC; preferred location for measuring the temperature is oral cavity. Any = occurrence of the event regardless of intensity grade.
Phase 1: Number of Participants Reporting Any Unsolicited Adverse Events (AEs)
时间窗: From Day 1 to Day 30
An unsolicited AE is an AE that is either not included in the list of solicited events or can be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Unsolicited AEs include both serious and non-serious AEs. Any = occurrence of the event regardless of intensity grade.
Phase 1: Number of Participants Reporting Any Unsolicited AEs
时间窗: From Day 61 to Day 90
An unsolicited AE is an AE that is either not included in the list of solicited events or can be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Unsolicited AEs include both serious and non-serious AEs. Any = occurrence of the event regardless of intensity grade.
Phase 1: Number of Participants Reporting Any Serious Adverse Events (SAEs) and AEs Leading to Withdrawal
时间窗: From Day 1 after the first dose to Day 241
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, abnormal pregnancy outcome or any other situation as determined by the investigator. An AE is any untoward medical occurrence (an unfavourable/unintended sign - including an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical study participant that is temporally associated with the study intervention. The AE may or may not be considered related to the study intervention. A participant is considered to have withdrawn from the study if no new study procedure has been performed or no new information has been collected for them since the date of withdrawal/last contact. Any = occurrence of the event regardless of intensity grade.
Phase 1: Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values
时间窗: At Day 8 compared to baseline (Day 1)
The safety laboratory data included haematological parameters \[hemoglobin, lymphocytes, platelets, neutrophils, and white blood cells (WBC)\] and biochemical parameters (Alanine Aminotransferase \[ALT\], Aspartate Aminotransferase \[AST\], Blood Urea Nitrogen and Creatinine). Categories reported when comparing Day 1 (baseline) and Day 8 haematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at baseline\>, \<range at timing\> (e.g. ALT, Within, Within). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Phase 1: Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values
时间窗: At Day 68 compared to baseline (Day 61)
The safety laboratory data included haematological parameters (hemoglobin, lymphocytes, platelets, neutrophils, and WBC) and biochemical parameters (ALT, AST, Blood Urea Nitrogen and Creatinine). Categories reported when comparing Day 61 (baseline) and Day 68 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at baseline\>, \<range at timing\> (e.g. ALT, Within, Within). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Unknown = No results are available for the corresponding laboratory parameter at the specific timepoint.
Phase 2: Incidence Rate of Confirmed Gonorrhea Cases
时间窗: From 1 month post-Dose 2 (Day 91) to 13 months post-Dose 2 (Day 451)
Incidence of first confirmed gonorrhea cases by positive Nucleic Acid Amplification Test (NAAT) at the anorectal and/or urogenital location were evaluated. The incidence rate (y/PT) of confirmed gonorrhea cases, expressed in terms of 100 person-years, was calculated as the number of confirmed gonorrhea cases (y) in a group, over the sum of individual person-times at risk (PT) in the same group, and multiplied by 100.
Phase 2: Number of Participants Reporting Any Solicited Administration Site Events
时间窗: From Day 1 to Day 7
Assessed solicited administration site events included injection site pain, erythema (redness), and swelling. Any = occurrence of the event regardless of intensity grade.
Phase 2: Number of Participants Reporting Any Solicited Administration Site Events
时间窗: From Day 61 to Day 67
Assessed solicited administration site events included injection site pain, erythema (redness), and swelling. Any = occurrence of the event regardless of intensity grade.
Phase 2: Number of Participants Reporting Any Solicited Systemic Events
时间窗: From Day 1 to Day 7
Assessed solicited systemic events included headache, fatigue (tiredness), myalgia (muscle pain), arthralgia (joint pain), and fever (pyrexia). Fever is defined as body temperature \>=38ºC; preferred location for measuring the temperature is oral cavity. Any = occurrence of the event regardless of intensity grade.
Phase 2: Number of Participants Reporting Any Solicited Systemic Events
时间窗: From Day 61 to Day 67
Assessed solicited systemic events included headache, fatigue (tiredness), myalgia (muscle pain), arthralgia (joint pain), and fever (pyrexia). Fever is defined as body temperature \>=38ºC; preferred location for measuring the temperature is oral. Any = occurrence of the event regardless of intensity grade.
Phase 2: Number of Participants Reporting Any Unsolicited AEs
时间窗: From Day 1 to Day 30
An unsolicited AE is an AE that is either not included in the list of solicited events or can be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Unsolicited AEs include both serious and non-serious AEs. Any = occurrence of the event regardless of intensity grade.
Phase 2: Number of Participants Reporting Any Unsolicited AEs
时间窗: From Day 61 to Day 90
An unsolicited AE is an AE that is either not included in the list of solicited events or can be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Unsolicited AEs include both serious and non-serious AEs. Any = occurrence of the event regardless of intensity grade.
Phase 2: Number of Participants Reporting Any SAEs and AEs Leading to Withdrawal
时间窗: From Day 1 after the first dose to Day 451
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, abnormal pregnancy outcome or any other situation as determined by the investigator. An AE is any untoward medical occurrence (an unfavourable/unintended sign - including an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical study participant that is temporally associated with the study intervention. The AE may or may not be considered related to the study intervention. A participant is considered to have withdrawn from the study if no new study procedure has been performed or no new information has been collected for them since the date of withdrawal/last contact. Any = occurrence of the event regardless of intensity grade.
Phase 2: Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values in HIV Negative (HIV-) Subset
时间窗: At Day 8 compared to baseline (Day 1)
The safety laboratory data included haematological parameters (hemoglobin, lymphocytes, platelets, neutrophils, and WBC) and biochemical parameters (ALT, AST, Blood Urea Nitrogen and Creatinine). Categories reported when comparing Day 1 (baseline) and Day 8 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at baseline\>, \<range at timing\> (e.g. ALT, Within, Within). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Phase 2: Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values for HIV Positive (HIV+) Subset
时间窗: At Day 8 compared to baseline (Day 1)
The safety laboratory data included haematological parameters (hemoglobin, absolute lymphocyte count, platelets, absolute neutrophil count, and WBC) and biochemical parameters (ALT, AST, Blood Urea Nitrogen and Creatinine). Categories reported when comparing Day 1 (baseline) and Day 8 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at baseline\>, \<range at timing\> (e.g. ALT, Within, Within). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Unknown = No results are available for the corresponding laboratory parameter at the specific timepoint.
Phase 2: Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values for HIV- Subset
时间窗: At Day 68 compared to baseline (Day 61)
The safety laboratory data included haematological parameters (hemoglobin, lymphocytes, platelets, neutrophils, and WBC) and biochemical parameters (ALT, AST, Blood Urea Nitrogen and Creatinine). Categories reported when comparing Day 61 (baseline) and Day 68 haematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at baseline\>, \<range at timing\> (e.g. ALT, Within, Within). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Unknown = No results are available for the corresponding laboratory parameter at the specific timepoint.
Phase 2: Number of Participants With Change From Baseline in Haematological and Biochemical Laboratory Values HIV+ Subset
时间窗: At Day 68 compared to baseline (Day 61)
The safety laboratory data included haematological parameters (hemoglobin, absolute lymphocyte count, platelets, absolute neutrophil count, and WBC) and biochemical parameters (ALT, AST, Blood Urea Nitrogen and Creatinine). Categories reported when comparing Day 61 (baseline) and Day 68 hematological and biochemical laboratory results are defined as follows: \<parameter\>, \<range at baseline\>, \<range at timing\> (e.g. ALT, Within, Within). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Unknown = No results are available for the corresponding laboratory parameter at the specific timepoint.
次要结局
- Phase 2: Incidence Rates of Confirmed Gonorrhea Cases With and Without Chlamydia Trachomatis Co-infection(From 1 month post-Dose 2 (Day 91) to 13 months post-Dose 2 (Day 451))
- Phase 2: Incidence Rates of Symptomatic and Confirmed Gonorrhea Cases(From 1 month post-Dose 2 (Day 91) to 13 months post-Dose 2 (Day 451))